The main objective of the study was to investigate the ability of frequency-domain photothermal radiometry (PTR) and modulated luminescence (LUM) to detect secondary caries lesions on the walls of restorations (wall lesions). Changes in experimental PTR-LUM signals due to sequential demineralization on entire vertical walls of sectioned tooth samples were investigated. In addition, transverse micro-radiography (TMR) analysis (used as a gold standard) was conducted to measure the degree of demineralization that occurred in each sample. Statistical correlation between TMR results and PTR-LUM signals was determined using Pearson’s correlation coefficient. LUM signals were found to be dominated by the scattered component of the incident laser beam. The more clinically relevant cases of localized demineralization and remineralization on vertical walls were also investigated to examine whether PTR-LUM signals are sensitive to demineralization and remineralization of much smaller areas. The overall results demonstrated that PTR-LUM is sensitive to progressive demineralization and remineralization on vertical walls of sectioned tooth samples.